Pentamidine, in the form of its hydrochloride salt, was first discovered by Ewins et al., as shown in U.S. Pat. No. 2,277,861. Pentamidine and other related compounds were found to have trypanocidal properties. However, pentamidine was initially available only in the form of its hydrochloride salt, which is substantially water insoluble. Because of the therapeutically beneficial results which could be derived from pentamidine, a need arose for water soluble salts of pentamidine. U.S. Pat. No. 2,410,796 to Newberry et al., is directed to such water soluble salts, particularly hydroxy-ethane sulfonic acid salt and hydroxy-propane sulfonic acid salt of pentamidine. The former compound is generally referred to as pentamidine isethionate.
Pentamidine isethionate is presently marketed by LyphoMed, Inc. under the trademark Pentam, for intravenous and intramuscular injection, and is indicated for the treatment of pneumonia due to pneumocystis carinii, the latter ailment typically being referred as "PCP". The importance of pentamidine isethionate has recently dramatically increased due to the marked increase of patients suffering from PCP. The increase in the afflicted patient population is an unfortunate consequence of the increasing presence of the Acquired Immunodeficiency Syndrome ("AIDS"). It is now estimated that approximately 70 percent of all AIDS patients contract PCP. Because of the high incidence of PCP in AIDS patients, pentamidine isethionate has found utility not only in the treatment of PCP, but also for prophylaxis, in preventing the initial onset or recurrence of PCP, especially in AIDS patients.
An unfortunate side effect of pentamidine isethionate is its toxicity. Some fatalities have been attributed to severe hypotension, hypoglycemia, and cardiac arrhythmias in patients treated with pentamidine isethionate, through both intramuscular and intravenous routes. Because of the concern over the potential toxicity of pentamidine isethionate, a need has arisen for a replacement for pentamidine isethionate which may minimize the potential undesirable side effects associated with the use of the drug.